Gene Therapy, back for good
• Some 2015-2016 Gene Therapy deals:• Celgene – Juno $1B (Cancer and
autoimmune diseases)• Vertex – CRISPR $2.6B (Gene Editing
for genetic diseases)• BMS – UniQure $2.3B
(cardiovascular)• Genzyme – Voyager $845M (CNS)• Amgen – Kite $1.1B (Cancer and
autoimmune diseases)• BioGen – Upenn $2B (Genetic
diseases)
• Some 2015-2016 Gene Therapy IPOs:• Nantkwest $238.3M (Cancer)
• Cellectis $228M (Gene Editing, Cancer)
• AdaptImmune $191.3M (Cancer)
• Spark $185.2M (Genetic Diseases)
• RegenexBIO $159.4M (Genetic diseases)
• Voyager $80.5M (CNS)
Some morenumbers:
What is Gene Therapy?
• Therapeutics that contain DNA and/or RNA
• Hope for a “once and for all” cure
• A “natural” therapy
First approved U.S. trial
conducted at the NIH
1990 2008
Positive results in the treatment
Leber’s Congenital Amaurosis
1999 2002
First fatality reported in a trial for the treatment of ornithine transcarbamylasedeficiency(Jesse Gelsinger)
Leukemiareported in X-SCID trial
2011
Limited positive results in the AAV8 Hemophilia B trial
2010
2012
First AAV based drug approved in
EU
Gene Therapy Ups and Downs
2014
First Genome Editing
human trial (ZFN, HIV)
2013
Successful T cell Gene Therapy for
Acutelymphocytic
leukemia (ALL)
2015
Successful Universal CAR-T
therapy (ALL)
2016
Gene Therapy hottest fields
Adeno-Associated Viral vector (AAV)
- ssDNA vector– stable and relatively easy to produce
- Non-pathogenic - 70-80% of human population have
been exposed
- Gutted design - all viral genes are removed from the
vector
- Approved therapeutic in E.U. over 30 clinical trials in
US and E.U
AAV Gene Therapy
- UniQure
- 4DMT
- Spark
- Avalanche
- AGTC
- Celladon
- Voyager
- Asklepios
- Dimension
- Audentes
- Genethon
- Regenerex
Companies to follow:
Hemophilia
Choroideremia
Genome Editing
Site specific manipulation of the genome:
• Gene Correction
• Gene insertion
• Gene Deletion
Leading platforms:• CRISPR• TALEN• ZFN• Mega-TAL
Gene Editing for Gene Therapy
HIV
Cancer
- Sangamo
- Cellectis
- CRISPR
- Editas
- Intellia
- Caribou
- Precision
Companies to follow:
Gene Immunotherapy
Gene Immunotherapy
- Kite
- Juno
- Celgene
- Bellicum
- Nantkwest
- Ziopharm
- Unum
Companies to follow:
Adenoviral
Vector
Retroviral
VectorLentiviral
Vector
Zinc
FingersTALENs
CRISPR
AAV
Genome Editing
LogicBio
12
Gene Therapy Gene Editing
AAV
No nuclease
GeneRide
No promoter
In vivo
AAV-LK03 transduces human cells over 10x better than clinically relevant AAV8
FRG humanized mice
1E6-1E8 variants1 variants – AAV-LK03
Lisowski et al – Nature, February 2014
Screen for Novel Vector with Superior Tropism for Primary Human Hepatocytes.
14
ITR
hF92A
5’ homology arm to Alb 3’ homology arm to Alb
… …Wild-type Alb locus
Stop
+Protein P hF9Alb 2A
DNA
…Targeted Alb locus …hF92A
RNA Fused mRNA Alb 2A hF9
Promotorless gene targeting without nucleases
Barzel et al., Nature 2015
GeneRide™ Technology
15
High and stable hF9 plasma levels
Neonates Adults
Preclinical Proof of ConceptHemophilia B
Barzel et al., Nature 2015
16
Normal light conditionPhototherapy treatment
P 8P 4
AAV donorDNA injection
P 30
Analysis
P8 Blue
0 105 15 20 25
25
0
50
75
100
421 3Days Months
Still alive and well at 12 months ***
% S
urv
ival
MUT P0-P8 PT
MUT P0-P8 PT + P4 injection pAlb
n=7
n=6
Preclinical Proof of ConceptCrigler Najjar Syndrome
17
Balazs et al., Nature Immunology, 2013
0
5
10
15
20
25
30
35
40
control AAV inf no AAV inf
%C
D3
CD
4 c
ou
nt
Preclinical Proof of ConceptVectored Immunoprophylaxis
18
19
Stabilityin dividing tissues
Safety
Nucleases
AAV with promoterAdeno
Retro and Lenti
GeneRide™
GeneRide is most compatible for treating both kids and adults
Thank you!
